Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand.
Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand.
J Pharm Sci. 2024 Sep;113(9):2756-2763. doi: 10.1016/j.xphs.2024.06.011. Epub 2024 Jun 17.
Since eyedrops have conventionally been formulated in aqueous vehicles, ocular pharmacokinetic studies are generally performed using aqueous buffers to identify physicochemical properties of the drug and the vehicles that influence drug absorption. In recent years, biocompatible lipophilic vehicles are increasingly finding application in ocular drug delivery; however, the mechanism of drug penetration from these non-aqueous vehicles is poorly understood. This study aims to compare ocular penetration of the model lipophilic drug curcumin when incorporated into lipophilic vehicles. To elucidate whether intrinsic solubility in the lipophilic vehicle influences ocular penetration, a curcumin solution and suspension were prepared in medium chain triglycerides (MCT) and squalane, respectively. Ocular penetration and distribution of curcumin from both vehicles was compared and evaluated qualitatively and quantitatively ex vivo. Significantly greater and faster penetration was observed from the squalane suspension than from the MCT solution in all ocular tissues. Our results suggest that the ability of lipophilic drugs to partition out of lipophilic vehicles and into cell membranes, rather than their intrinsic solubility in the lipophilic vehicle, determines the rate and extent of their ocular penetration.
由于眼药水通常在水性载体中配制，因此眼药代动力学研究通常使用水性缓冲液来确定影响药物和载体吸收的理化性质。近年来，生物相容性亲脂性载体在眼部药物输送中的应用越来越广泛；然而，这些非水性载体中药物渗透的机制尚不清楚。本研究旨在比较将模型亲脂性药物姜黄素掺入亲脂性载体后的眼部渗透情况。为了阐明亲脂性载体中的固有溶解度是否会影响眼部渗透，分别在中链甘油三酯（MCT）和角鲨烷中制备了姜黄素溶液和混悬液。比较并评估了这两种载体中姜黄素的眼部渗透和分布情况。在所有眼部组织中，与 MCT 溶液相比，来自角鲨烷混悬液的渗透速度更快、程度更高。我们的结果表明，亲脂性药物从亲脂性载体中分配到细胞膜中的能力，而不是其在亲脂性载体中的固有溶解度，决定了它们眼部渗透的速度和程度。
